# High-content functional cancer drug testing on micro-cuboidal tumor dissections

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $601,999

## Abstract

ABSTRACT
The goal of this project is to perform high-content analysis of drug and immunotherapy responses on hundreds
of intact, live cultured fragments isolated from a single live tumor biopsy. In recent years, patient-derived tumor
“organoids” have shown great promise to predict drug responses for personalized cancer treatment.
Immunotherapy, including cellular immunotherapy, represents the next generation of cancer therapy, and many
of the relevant drugs act on the local tumor microenvironment (TME). There is a pressing need for functional
testing platforms that use human, intact and live tumor tissue to better predict traditional and immunotherapy
responses. Such platforms should also retain as much of the native TME as possible. Present high-throughput
testing platforms that have some of these features, e.g. based on patient-derived tumor organoids, require a
growth step that alters the TME. On the other hand, the micro-dissection of tumor tissue into “spheroids” that
contain the TME intact has shown promising responses to immunomodulators on native immune cells. We
propose a microfluidic platform that enables drug treatment, exogenous T cell therapy, and high-content
analysis using hundreds to thousands of similarly sized, precision-sliced cuboidal micro-tissues (CµTs)
produced from a single tumor sample.
Here we propose a combination of two methodologies to demonstrate the feasibility of our approach: 1) precision
slicing methodology that will produce large numbers of cuboidal micro-tissues (CµTs) from a single tumor
biopsy; and 2) microfluidic trapping of the CµTs in a multi-well platform, allowing for drug application to each
individual CµT or groups of CµTs. We will be able to obtain several hundred patient-derived CµTs from each
tumor resection. The size of the CµTs (initially 400 µm×400 µm×400 µm) will be reproducible and chosen to
optimize viability and retention of the TME. As the CµTs are cultured, their cuboidal shape will relax into a more
rounded one. We will study the viability of the CµTs and their TME composition as a function of size in various
culture conditions, including collagen gels.
We will focus on breast cancer immunotherapy using a syngeneic mouse breast tumor model. For this Aim, we
will deliver various concentrations and combinations of immunomodulatory drugs, including antibody-based
drugs, to breast tumor CµTs in the microfluidic device, and examine the effects on the resident immune system.
We will assess cytokine production and use high-content immunohistochemistry and bioinformatics analysis to
assess immune cell engagement with different cell types as well as cell death. We will apply the platform to
deliver immune checkpoint inhibitors (CTLA4, PD-L1, PD-1) and other immunomodulators (such as IL-10) and
examine the effect on the immune state, cell death, and the behavior of resident T cells (activation and
localization). In the R33 phase we plan on applying our microfluidic platform to CµTs obtained from bre...

## Key facts

- **NIH application ID:** 10025143
- **Project number:** 1R21CA251952-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ALBERT FOLCH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $601,999
- **Award type:** 1
- **Project period:** 2020-08-06 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025143

## Citation

> US National Institutes of Health, RePORTER application 10025143, High-content functional cancer drug testing on micro-cuboidal tumor dissections (1R21CA251952-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10025143. Licensed CC0.

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